The present invention relates to a novel compound, 6,6-ethylenedioxy-22R-hydroxy-2R, 3S-isopropylidenedioxy-5.alpha.-cholest-23-yne, useful as a synthetic intermediate for brassinolide.
2. Description of the Prior Art
Brassinolide, (22R,23R,24S)-2.alpha.,3.alpha.,22,23-tetrahydroxy-24-methyl-B-homo-7-oxa- 5.alpha.-cholestan-6-one, is a naturally occurring steroid known to have potent plant-growth promoting activity and is expected to present a wide variety of applications in agriculture etc. A number of attempts have been made to develop an efficient process for the synthesis of brassinolide. Processes reported up until now, however, are accompanied, more or less, by certain drawbacks; e.g. use of steroid little found in nature as the starting material and low stereoselectivity, M. J. Thompson et al, Steroids 38 2864-2876 (1981); cumbersome preparation of the side chain, J. B. Siddall et al, J. Am. Chem. Soc. 102 6580-6581 (1980), K. Mori et al, Tetrahedron 38 2099-2109 (1982) and H. Nozaki et al, J. Am. Chem. Soc. 105 4491-4492 (1983); formation of by-products of little use, A. Fiecchi, J. Chem. Soc. Perkin Trans. I 1983 383, M. Anastasia et al, J. Chem. Soc. Perkin Trans. I 1983 2365-2367 and J. Tsuji et al, 45 th Yuki-Gosei Symposium (1-7), June 7, 1984; and involvement of many steps, N. Ikekawa et al, J. Chem. Soc. Chem. Comn. 1980, 962-964 and M. Anastasia et al, J. Org. Chem. 49 4297-4300 (1984). Furthermore, the overall yield of brassinolide is quite low in these known processes.
M. Sakakibara and K. Mori reported, in Agric. Biol. Chem., 47 (3) 663-664 (1983), an alternative process for the preparation of brassinolide from stigmasterol abundantly available from natural resources, which is rather simple as compared with other such processes disclosed in the literature mentioned above. The process is reported to involve a step of reacting an aldehyde A with 1,1-dibromo-3-methyl-1-butene and n-butyl lithium to give the acetylene alcohols B1 and B2, as is shown by the following scheme: ##STR1## The aldehyde A is also reported to have been prepared by the method described in the reference cited there, i.e. K. Mori et al, Tetrahedron, 38, 2099 (1982). It is also reported that the overall yield of brassinolide was improved to 3.0% and that the 22S- and 22R-alcohols, B1 and B2, were separable by HPLC.
In following up these alleged results, we have found the following facts:
(1) The starting material for the synthesis of the aldehyde A and, hence the aldehyde A itself, does not have the isopropylidenedioxy residue but the sec-butylidenedioxy residue, and therefore the acetylene alcohols B1 and B2 derived from the aldehyde A are and not of the formula shown above but of the formula (III) and (IV), respectively: ##STR2## (i.e. 6,6-ethylenedioxy-22R (or 22S)-hydroxy-2R, 3S-sec.-butylidenedioxy-5.alpha.-cholest-23yne). This will be demonstrated in Referential Example 3 below. It has also been found that the acetylene alcohol III gives two spots in thin layer chromatography (TLC plate: Merck Silica Gel 60F254 Precoat; Eluent: acetone:chloroform=1:25; Development up to ca. 7 cm followed by coloration with sulfuric acid) and has a molecular weight, as determined by mass spectroscopy, of 528; PA1 (2) A mixture of the acetylene alcohol III and its 22S-isomer IV does not crystallize, which is not desirable from the viewpoint of work-up operations like separation and purification; PA1 (3) The mixture, being a mixture of four isomers, cannot easily be separated even by means of column chromatography.